The Hepatitis Delta Virus (HDV) is a small RNA virus which replicates only in patients who are concurrently infected with hepatitis B virus (HBV). Delta hepatitis is endemic particularly in countries in the Mediterranean basin. In other parts of the world, HDV infection occurs among intravenous drug addicts and persons who receive multiple blood transfusion. HDV superinfection in a chronic HBV carrier often leads to severe chronic hepatitis and cirrhosis, whereas acute HDV and HBV co-infection is frequently associated with fulminant hepatitis. Diagnosis is usually based on the detection of HDV antigen in liver tissue and antibody to HDV (anti-HD) in serum. Nowadays, HDV antigen can also be detected in serum using immunoblot assay. The presence of HDV-RNA can now be confirmed by molecular biology techniques including polymerase chain reaction (PCR). Interestingly, up to 50% of patients with chronic HDV infection have in the serum autoantibodies against microsomal antigens of the human liver and kidney (LKM) and antibodies against the basal cell layer of the rat forestomach. Therapeutic approaches including interferon therapy and liver transplantation are still under discussion. This review discusses in detail some of the main features of chronic HDV infection.